부산대학교 도서관

Various statistical methods can be applied when undertaking analyses of association of human disease and traits with rare genetic variants in next generation sequence (NGS) datasets, depending on the phenotype of interest. The choice of open source software tools and packages to implement such methods are plentiful with varying features and available options, which makes it challenging for the end users to choose between different alternatives. The literature was searched to identify tools developed for rare variant association analysis in NGS datasets and a summary compiled. Each tool has its own features, advantages and limitations when considering factors such as efficiency, stability, user documentation and support. EPACTS, RVtests, and VAT are widely used standalone packages that offer flexible, efficient implementation of many statistical tests together with quality control procedures. R packages including SKAT and SAIGE-GENE are useful as they can utilise freely available libraries for data analysis and visualization. It is important for any existing packages to implement tests newly proposed in the literature to stay relevant in terms of use, but very few of them are updated actively. The results of this comparative review will provide guidance to researchers wishing to undertake genetic association analyses with rare variants using NGS data, and allow them to choose a suitable tool.